糖尿病肾病早期miRNAs表达谱分析

MiRNAs Expression Profiles in the Early Stage of Diabetic Mice

目的:探讨mi RNAs在糖尿病肾病(DN)早期的表达谱的改变,从而为其在DN发病机制中的研究提供有力的平台。方法:腹腔单剂注射链脲佐菌素(streptozotocin,STZ,150 mg/kg)建立小鼠糖尿病模型,检测对照组和糖尿病小鼠尿白蛋白排泄率,采用PAS染色观察肾脏组织学的改变;MicroRNAs微阵列分析采用单通道Cy5荧光标记法,分析对照组和糖尿病mi RNAs表达谱,利用GO分析对差异表达mi RNAs进行靶通道测定。结果:糖尿病组白蛋白排泄率显著高于对照组(P<0.05);PAS染色提示糖尿病组小鼠肾小球内大量细胞外基质积聚,系膜区明显增宽,符合DN早期的病理改变。糖尿病组共检测出128个mi RNAs,其中显著上调者分别mi R-34a,mi R-214,mi R-2132;显著下调者为mi R-2143,mi R-1970,mi R-703;以上差异有统计学意义mi RNAs参与细胞周期、细胞黏附、凋亡、小G蛋白介导的细胞信号传导的调控。结论:DN早期mi RNAs表达谱发生差异有统计学意义,微阵列技术为DN发病机制的研究提供了全新的研究策略。

Objective：To investigate the differences in MicroRNA（miRNAs） profiles in renal cortex between diabetic mice and controls.Methods：Diabetic mice models were established by single dose of intraperitoneal administration of streptozotocin（STZ） in mice.Mice which were given the same dose of normal saline were set as controls.Blood glucose levels and urine albumin excretion（UAE） were measured in all mice and histological changes in the glomeruli were observed by PAS stainings.MiRNAs expression profiles were analyzed in renal cortex by microRNA array using single channel labeled with Cy5.The different miRNAs were subjected to gene ontology（GO） analysis to predict the target pathway.Results：UAE increased significantly,which were in accordance with pathological changes such as deposition of extracellular matrix and mesangial expansion in diabetic glomeruli.Total 128 miRNAs were detected in renal cortex.Expressions of miR-34a,miR-214,miR-2132 were significantly up regulated miRNAs,while expressions of miR-2143,miR-1970 and miR-703 were remarkably down regulated.These miRNAs were involved in apoptosis,cell cycle,cell adhesion and small GTPase mediated signal transduction.Conclusion：The change of miRNAs profiles was statistically significant in early stage in diabetic kidney.MiRNAs array provided a novel strategy in our understanding of genetic regulatory pathways underlying DN.